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Air can become trapped within the subcutaneous layer of the cervicofacial area, a condition known as subcutaneous emphysema (SE), unexpectedly after routine dental procedures. SE can worsen by extending superiorly to the peri-orbital region and inferiorly to the thorax and abdomen along the fascial planes. Upward progression can result in cavernous sinus thrombosis. Conversely, downward progression can cause a variety of complications such as pneumothorax, mediastinitis, and compression of the venous trunks. The presence of these conditions highlights the significance of prompt identification, precise diagnosis to ascertain the need for immediate intervention, and suitable management to prevent additional unfavorable consequences., (©Operative Dentistry, 2024.)

Background: There remain concerns about the safety and functional benefit of laparoscopic pylorus-preserving gastrectomy (LPPG) compared with laparoscopic distal gastrectomy (LDG). This study evaluated short-term outcomes of a randomized clinical trial (RCT) comparing LPPG with LDG for gastric cancer., Methods: The Korean Laparoendoscopic Gastrointestinal Surgery Study (KLASS)-04 trial was an investigator-initiated, open-label, parallel-assigned, superiority, multicentre RCT in Korea. Patients with cT1N0M0 cancer located in the middle third of the stomach at least 5 cm from the pylorus were randomized to undergo LPPG or LDG. Participants, care givers and those assessing the outcomes were not blinded to group assignment. Outcomes were 30-day postoperative morbidity rate and death at 90 days., Results: Some 256 patients from nine institutions were randomized (LPPG 129 patients, LDG 127 patients) between July 2015 and July 2017 and outcomes for 253 patients were analysed. Postoperative complications within 30 days were seen in 19.3 and 15.5 per cent in the LPPG and LDG groups respectively (P = 0·419). Postoperative pyloric stenosis was observed in nine (7.2 per cent) and two (1·5 per cent) patients in the LPPG and LDG groups (P = 0·026) respectively. In multivariable analysis higher BMI was a risk factor for postoperative complications (odds ratio 1·17, 95 per cent c.i. 1·04 to 1·32; P = 0·011). Death at 90 days was zero in both groups., Conclusion: Postoperative complications and mortality was comparable in patients undergoing LPPG and LDG. Registration number: NCT02595086 (http://www.clinicaltrials.gov)., (© The Author(s) 2021. Published by Oxford University Press on behalf of BJS Society Ltd. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

There is a need for effective wound healing through rapid wound closure, reduction of scar formation, and acceleration of angiogenesis. Hydrogel is widely used in tissue engineering, but it is not an ideal solution because of its low vascularization capability and poor mechanical properties. In this study, gelatin methacrylate (GelMA) was tested as a viable option with tunable physical properties. GelMA hydrogel incorporating a vascular endothelial growth factor (VEGF) mimicking peptide was successfully printed using a three-dimensional (3D) bio-printer owing to the shear-thinning properties of hydrogel inks. The 3D structure of the hydrogel patch had high porosity and water absorption properties. Furthermore, the bioactive characterization was confirmed by cell culture with mouse fibroblasts cell lines (NIH 3T3) and human umbilical vein endothelial cells. VEGF peptide, which is slowly released from hydrogel patches, can promote cell viability, proliferation, and tubular structure formation. In addition, a pig skin wound model was used to evaluate the wound-healing efficacy of GelMA-VEGF hydrogel patches; the results suggest that the GelMA-VEGF hydrogel patch can be used for wound dressing., (Creative Commons Attribution license.)

Introduction: The pelvic floor muscle (PFM) could affect female sexual functions. The hip muscles are morphologically and functionally linked to PFM and are important elements of female sexual attraction., Aim: To determine the relationship between female sexual function and hip muscle strength and PFM functions in women with stress urinary incontinence (SUI)., Methods: A total of 42 women with SUI were recruited in this study. Female sexual function was measured using the pelvic organ prolapse urinary incontinence sexual function questionnaire (PISQ). PFM functions were measured using a perineometer. Hip muscle strength was measured using a Smart KEMA tension sensor. The relationship between female sexual function and PFM function and hip muscle strength was assessed using Pearson correlation coefficients and multiple regression analyses with forward selection., Main Outcome Measures: PISQ score, PFM functions (strength and endurance), and strength of hip extensor, abductor, and adductor were the main outcome measures., Results: For the behavioral/emotive domain in the PISQ, hip extensor strength (r = 0.452), PFM strength (r = 0.441), PFM endurance (r = 0.362), and hip adductor strength (r = 0.324) were significantly correlated and hip extensor strength emerged in multiple regression. For the physical domain in the PISQ, hip abductor strength (r = 0.417), PFM endurance (r = 0.356), hip adductor strength (r = 0.332), and PFM strength (r = 0.322) were significantly correlated and hip abductor strength entered in multiple regression. For partner-related domain in the PISQ, hip adductor (r = 0.386) and abductor strength (r = 0.314) were significantly correlated and hip adductor strength appeared in multiple regression. For the PISQ total score, hip extensor strength (r = 0.484), PFM endurance (r = 0.470), hip adductor strength (r = 0.424), hip abductor strength (r = 0.393), and PFM strength (r = 0.387) were significantly correlated and hip extensor strength and PFM endurance emerged in multiple regression., Conclusion: The female sexual function could be related to not only PFM functions but also hip muscle strength in women with SUI. Hwang UJ, Lee MS, Jung SH, Ahn SH, Kwon OY. Relationship Between Sexual Function and Pelvic Floor and Hip Muscle Strength in Women With Stress Urinary Incontinence. Sex Med 2021;9:100325., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

We investigated the relationship between the prognostic importance of anatomic tumour burden and subtypes of breast cancer using data from the Korean Breast Cancer Registry Database. In HR+/HER2+ and HR-/HER2-tumours, an increase in T stage profoundly increased the hazard of death, while the presence of lymph node metastasis was more important in HR+/HER2+ and HR-/HER2+ tumours among 131,178 patients with stage I-III breast cancer. The patterns of increasing mortality risk and tumour growth (per centimetre) and metastatic nodes (per node) were examined in 67,038 patients with a tumour diameter ≤ 7 cm and < 8 metastatic nodes. HR+/HER2- and HR-/HER2- tumours showed a persistent increase in mortality risk with an increase in tumour diameter, while the effect was modest in HER2+ tumours. Conversely, an increased number of metastatic nodes was accompanied by a persistently increased risk in HR-/HER2+ tumours, while the effect was minimal for HR-/HER2- tumours with > 3 or 4 nodes. The interactions between the prognostic significance of anatomic tumour burden and subtypes were significant. The prognostic relevance of the anatomic tumour burden was non-linear and highly dependent on the subtypes of breast cancer.

Background and Purpose: Carotid artery stent placement is widely performed for treatment of carotid stenosis. The purpose of this study is to present our observations on cerebral vasoconstriction in ipsilateral anterior circulation during immediate poststenting angiography in patients with near-total occlusion of the proximal ICA., Materials and Methods: We retrospectively reviewed patient data from December 2008 to December 2018. There were 28 patients with carotid near-total occlusion. Two neuroradiologists reviewed the final cerebral angiographic finding of carotid artery stent placement to evaluate the presence of vasoconstriction or vasodilation., Results: A total of 28 patients with near-total occlusion (mean ± standard deviation age, 69.0 ± 6.5 years; 92.9% male) were analyzed. Ten patients showed vasoconstriction in the treated territory, and 18 patients did not show vasoconstriction after carotid artery stenting. There were no statistically significant differences in comorbidity, frequency of symptomatic lesions, antiplatelet medication, mean procedure time, and initial NIHSS and baseline modified Rankin scale scores between the 2 groups. However, vasoconstriction is more likely to happen in patients with isolated territory from the contralateral anterior and posterior circulation (66.7% in the isolated territory group and 12.5% in the not-isolated territory group; P  < .05). No headache or neurologic deficit was noted in all 10 patients with cerebral vasoconstriction., Conclusions: Cerebral vasoconstriction may occur after carotid artery stenting more frequently than expected. It occurs more frequently in patients with near-total occlusion and with isolation of the cerebral circulation. A large-scale study is necessary to assess the clinical implications of cerebral vasoconstriction after carotid artery stenting., (© 2020 by American Journal of Neuroradiology.)

Background and Purpose: The role of collateral imaging in selecting patients for endovascular thrombectomy beyond 6 hours from onset has not been established. To assess the comparative utility of collateral imaging using multiphase CTA in selecting late window patients for EVT., Materials and Methods: We used data from a prospective multicenter observational study in which all patients underwent imaging with multiphase CT angiography as well as CTP. Two blinded reviewers evaluated patients' eligibility for endovascular thrombectomy using published collateral imaging (multiphase CTA) criteria compared with CTP using the selection criteria of the Clinical Mismatch in the Triage of Wake Up and Late Presenting Strokes Undergoing Neurointervention with Trevo (DAWN) and Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3 (DEFUSE-3) trials. CTP images were processed using automated commercial software. The outcomes of patients eligible for endovascular thrombectomy according to multiphase CTA, DAWN, or DEFUSE-3 criteria were compared using multivariable logistic regression modeling. Model characteristics were compared using the C-statistic for the receiver operating characteristic curve, the Akaike information criterion, and the Bayesian information criterion., Results: Eighty-six patients presented beyond 6 hours from onset/last known well (median, 9.6 hours; interquartile range, 4.1 hours). Thirty-five patients (40.7%) received endovascular thrombectomy, of whom good functional outcome (90-day mRS, 0-2) was achieved in 16/35 (47%). Collateral-based imaging paradigms significantly modified the treatment effect of endovascular thrombectomy on 90-day mRS 0-2 ( P interaction = .007). The multiphase CTA-based regression model best fit the data for the 90-day outcome (C-statistic, 0.86; 95% CI, 0.77-0.94) and was associated with the least information loss (Akaike information criterion, 95.7; Bayesian information criterion, 114.9) compared with CTP-based models., Conclusions: The collateral-based imaging paradigm using multiphase CTA compares well with CTP in selecting patients for endovascular thrombectomy in the late time window., (© 2020 by American Journal of Neuroradiology.)

Aim: To evaluate the correlation between the apparent diffusion coefficient (ADC) and various histopathological parameters in small hepatocellular carcinomas (HCCs)., Materials and Methods: In 143 surgically resected small HCCs, the mean and minimum ADC values, tumour-to-liver ADC ratio, and normalised ADC (ADC of the HCC/ADC of the spleen) were correlated to the tumour grade, microvascular invasion (MVI), cellularity, fatty change, degree of fibrosis, and lymphocytic infiltration using linear regression analysis, the Wilcoxon rank sum test, or Spearman's rank correlation., Results: No significant correlation was found between the ADC parameters and tumour grade. In the univariate analysis, the ADC ratio of the tumour was significantly correlated with MVI as well as the degree of fibrosis and lymphocyte infiltration of the HCC (p=0.017, 0.042, and 0.002, respectively). The ADC of the tumour was significantly correlated with the degree of lymphocyte infiltration of the HCC (p=0.049). In the multivariate analysis, the ADC ratio of the tumour was an independent parameter for MVI and the degree of lymphocyte infiltration of the HCC (p=0.034 and <0.001, respectively), and the ADC of the tumour was an independent parameter for the degree of lymphocyte infiltration of the HCC (p=0.009). There was no significant correlation between the other ADCs and pathological tumour parameters., Conclusion: The tumour grade of small HCCs was not correlated with ADC parameters. The tumour-to-liver ADC ratio was a significant independent parameter for the degree of lymphocyte infiltration and MVI of small HCCs., (Copyright © 2019 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

The plasma n-3 fatty acid level was 26.2% lower in patients with osteoporotic hip fracture than in those with osteoarthritis. In all patients, n-3 fatty acid was positively associated with bone mineral density and inversely associated with tartrate-resistant acid phosphatase-5b level in bone marrow aspirates, reflecting the bone microenvironment., Introduction: Despite the potential beneficial role of n-3 fatty acid (FA) on bone metabolism, the specific mechanisms underlying these effects in humans remain unclear. Here, we assessed whether the plasma n-3 level, as an objective indicator of its status, is associated with osteoporosis-related phenotypes and bone-related markers in human bone marrow (BM) samples., Methods: This was a case-control and cross-sectional study conducted in a clinical unit. n-3 FA in the blood and bone biochemical markers in the BM aspirates were measured by gas chromatography/mass spectrometry and immunoassay, respectively. BM fluids were collected from 72 patients who underwent hip surgery because of either osteoporotic hip fracture (HF; n = 28) or osteoarthritis (n = 44)., Results: After adjusting for confounders, patients with HF had 26.2% lower plasma n-3 levels than those with osteoarthritis (P = 0.006), and each standard deviation increment in plasma n-3 was associated with a multivariate-adjusted odds ratio of 0.40 for osteoporotic HF (P = 0.010). In multivariate analyses including all patients, a higher plasma n-3 level was associated with higher bone mass at the lumbar spine (β = 0.615, P = 0.002) and total femur (β = 0.244, P = 0.045). Interestingly, the plasma n-3 level was inversely associated with the tartrate-resistant acid phosphatase-5b level (β = - 0.633, P = 0.023), but not with the bone-specific alkaline phosphatase level, in BM aspirates., Conclusions: These findings provide clinical evidence that n-3 FA is a potential inhibitor of osteoclastogenesis that favors human bone health.

Analyses using the largest Korean cohort of adrenal incidentaloma (AI) revealed that subtle cortisol excess in premenopausal women and reduced dehydroepiandrosterone-sulfate (DHEA-S) in postmenopausal women and men are associated with bone mineral density (BMD) reduction in Asian patients with subclinical hypercortisolism (SH)., Introduction: Few studies evaluated bone metabolism in Asians with SH. We investigated associations of cortisol and DHEA-S, an adrenal androgen, with BMD in Asians with AI, with or without SH., Methods: We used cross-sectional data of a prospective multicenter study from Korea. We measured BMD, bone turnover markers, cortisol levels after 1-mg dexamethasone suppression test (1-mg DST), DHEA-S, and baseline cortisol to DHEA-S ratio (cort/DHEA-S) in 109 AI patients with SH (18 premenopausal, 38 postmenopausal women, and 53 men) and 686 with non-functional AI (NFAI; 59 premenopausal, 199 postmenopausal women, and 428 men)., Results: Pre- and postmenopausal women, but not men, with SH had lower BMDs at lumbar spine (LS) than those with NFAI (P = 0.008~0.016). Premenopausal women with SH also had lower BMDs at the hip than those with NFAI (P = 0.009~0.012). After adjusting for confounders, cortisol levels after 1-mg DST demonstrated inverse associations with BMDs at all skeletal sites only in premenopausal women (β = - 0.042~- 0.033, P = 0.019~0.040). DHEA-S had positive associations with LS BMD in postmenopausal women (β = 0.096, P = 0.001) and men (β = 0.029, P = 0.038). The cort/DHEA-S had inverse associations with LS BMD in postmenopausal women (β = - 0.081, P = 0.004) and men (β = - 0.029, P = 0.011). These inverse associations of cort/DHEA-S remained significant after adjusting for cortisol levels after 1-mg DST (β = - 0.079~- 0.026, P = 0.006~0.029). In postmenopausal women, the odds ratios of lower BMD by DHEA-S and cort/DHEA-S was 0.26 (95% CI, 0.08-0.82) and 3.40 (95% CI, 1.12-10.33), respectively., Conclusion: Subtle cortisol excess in premenopausal women and reduced DHEA-S in postmenopausal women and men may contribute to BMD reduction in Asians with SH.

Background and Purpose: Intracranial hemorrhage is a known complication following endovascular thrombectomy. The radiologic characteristics of a CT scan may assist with hemorrhage risk stratification. We assessed the radiologic predictors of intracranial hemorrhage following endovascular therapy using data from the INTERRSeCT (Identifying New Approaches to Optimize Thrombus Characterization for Predicting Early Recanalization and Reperfusion With IV Alteplase and Other Treatments Using Serial CT Angiography) study., Materials and Methods: Patients undergoing endovascular therapy underwent baseline imaging, postprocedural angiography, and 24-hour follow-up imaging. The primary outcome was any intracranial hemorrhage observed on follow-up imaging. The secondary outcome was symptomatic hemorrhage. We assessed the relationship between hemorrhage occurrence and baseline patient characteristics, clinical course, and imaging factors: baseline ASPECTS, thrombus location, residual flow grade, collateralization, and clot burden score. Multivariable logistic regression with backward selection was used to adjust for relevant covariates., Results: Of the 199 enrolled patients who met the inclusion criteria, 46 (23%) had an intracranial hemorrhage at 24 hours. On multivariable analysis, postprocedural hemorrhage was associated with pretreatment ASPECTS (OR, 1.56 per point lost; 95% CI, 1.12-2.15), clot burden score (OR, 1.19 per point lost; 95% CI, 1.03-1.38), and ICA thrombus location (OR, 3.10; 95% CI, 1.07-8.91). In post hoc analysis, clot burden scores of ≤3 (sensitivity, 41%; specificity, 82%; OR, 3.12; 95% CI, 1.36-7.15) and pretreatment ASPECTS ≤ 7 (sensitivity, 48%; specificity, 82%; OR, 3.17; 95% CI, 1.35-7.45) robustly predicted hemorrhage. Residual flow grade and collateralization were not associated with hemorrhage occurrence. Symptomatic hemorrhage was observed in 4 patients., Conclusions: Radiologic factors, early ischemia on CT, and increased CTA clot burden are associated with an increased risk of intracranial hemorrhage in patients undergoing endovascular therapy., (© 2019 by American Journal of Neuroradiology.)

Daclatasvir plus asunaprevir (DCV+ASV) treatment is an all-oral direct-acting antiviral (DAA) therapy for the genotype 1b HCV-infected patients. In this study, we investigated how resistance-associated substitutions (RASs) evolved after treatment failures and assessed the effect of those substitutions on viral fitness. Sequencing of NS5A and NS3 revealed typical RASs after treatment failures. Interestingly, the RASs of NS3 reverted to the wild-type amino acid within 1 year after treatment failures. However, the RASs of NS5A were stable and did not change. The effect of NS5A and NS3 RASs on viral RNA replication was assessed after mutagenic substitution in the genotype 1b HCV RNA. Among single substitutions, the effect of D168V was more substantial than the others and the effect of the triple mutant combination (D168V+L31V+Y93H) was the most severe. The RAS at NS5A Y93 affected both viral RNA replication and virus production. Finally, the effect of trans-complementation of NS5A was demonstrated in our co-transfection experiments and these results suggest that such a trans-complementation effect of NS5A may help maintain the NS5A RASs for a long time even after cessation of the DAA treatment. In conclusion, the results from this investigation would help understand the emergence and persistence of RASs., (© 2018 John Wiley & Sons Ltd.)

Vesatolimod is an oral agonist of toll-like receptor 7 designed to minimize systemic exposure and side effects. We assessed the safety and efficacy of vesatolimod in viremic chronic hepatitis B (CHB) patients not currently on oral antiviral treatment (OAV) in a phase 2, multicentre, double-blind, randomized, placebo-controlled study. A total of 192 patients stratified by HBeAg status and alanine aminotransferase level were randomized 2:2:2:1 to receive oral vesatolimod (1-, 2- or 4-mg) or placebo once weekly for 12 weeks; tenofovir disoproxil fumarate (300-mg daily) was administered daily for 48 weeks. Efficacy was assessed by quantitative serum HBsAg decline at Week 24 from baseline. In addition to safety assessments, changes in whole-blood interferon-stimulated gene (ISG) transcripts and serum cytokines were explored. Most patients were male (64.1%) and HBeAg-negative (60.9%) at baseline. Among vesatolimod-treated patients, most (60.4%-69.1%) experienced ≥1 treatment-emergent adverse event; the majority were mild or moderate in severity. No clinically meaningful differences in HBsAg changes from baseline were observed between treatment groups. No patients experienced HBsAg loss, while 3 patients experienced HBeAg loss and hepatitis B e-antibody seroconversion at week 48. HBV DNA suppression rates were similar across all treatment arms at Week 24. ISG15 induction was dose-dependent and did not correlate with HBsAg changes. A small proportion of patients exhibited dose-dependent interferon-α induction that correlated with grade of influenza-like adverse events. Overall, vesatolimod is safe and well tolerated in CHB patients. Although consistent dose-dependent pharmacodynamic induction of ISGs was demonstrated, it did not result in clinically significant HBsAg decline., (© 2018 John Wiley & Sons Ltd.)

Despite ethnic differences in cortisol sensitivity, only one study in Caucasians has assessed trabecular bone score (TBS) in patients with subclinical hypercortisolism (SH). We showed that both subtle cortisol excess and reduced adrenal androgen may contribute to impaired bone quality in Asian women with SH., Introduction: One study in Caucasians has assessed trabecular bone score (TBS), an index of bone microstructure, in adrenal incidentaloma (AI) patients with subclinical hypercortisolism (SH). There are ethnic differences in cortisol sensitivities between Caucasian and Asian populations. We investigated the associations of cortisol and the adrenal androgen dehydroepiandrosterone-sulfate (DHEA-S) with TBS in AI patients with SH, adrenal Cushing's syndrome (CS), and nonfunctional AI (NFAI)., Methods: We measured TBS, cortisol levels after the overnight 1 mg dexamethasone suppression test (1 mg DST), and cortisol/DHEA-S in 61 patients with SH (30 men; 31 women), 19 with adrenal CS (4 men; 15 women), and 355 with NFAI (213 men; 142 women)., Results: After adjusting for confounders, the serum cortisol level after 1 mg DST was inversely correlated with TBS in men (β = -0.133, P = 0.045) and women (β = - 0.140, P = 0.048). Higher cortisol/DHEA-S ratio was associated with lower TBS in women (β = - 0.252, P < 0.001), but not men. This inverse association of cortisol/DHEA-S ratio in women remained statistically significant after adjusting for the serum cortisol level after 1 mg DST (β = - 0.221, P = 0.008). Compared with women with NFAI, women with SH had 2.2% lower TBS (P = 0.040). Deteriorated bone microstructure (TBS < 1.230) was associated with the serum cortisol level after 1 mg DST (odds ratio [OR], 2.18; 95% confidence interval [CI], 1.04-4.53) and cortisol/DHEA-S ratio (OR, 2.05; 95% CI, 1.03-4.08)., Conclusions: Subtle cortisol excess in both genders and reduced DHEA-S, especially in women, may contribute to impaired bone quality in Asian patients with SH.

Background: Sarcopenia is significantly associated with the degree of liver fibrosis. This study investigated the influence of sarcopenia on liver fibrosis in individuals with chronic hepatitis B., Methods: Data from the Korean National Health and Nutrition Examination Surveys 2008-2011 were analysed. The sarcopenia index (total appendicular skeletal muscle mass [kg]/body mass index [kg/m 2 ]) was calculated using dual-energy X-ray absorptiometry. Sarcopenia was defined as the lowest quintile sarcopenia index value (cut-offs: 0.89 for men and 0.58 for women). The fibrotic burden was assessed using the nonalcoholic fatty liver disease fibrosis score and fibrosis-4 index. Significant fibrosis was defined as the highest nonalcoholic fatty liver disease fibrosis score quartile and a fibrosis-4 index ≥2.67., Results: Among the 506 respondents with chronic hepatitis B (258 men and 248 women), the nonalcoholic fatty liver disease fibrosis score and fibrosis-4 index identified sarcopenia and significant fibrosis in 126 (24.9%) and 217 (42.9%), respectively. Sarcopenia was significantly associated with significant fibrosis, regardless of the fibrosis prediction model used (all P < 0.05). When the study population was stratified according to metabolic factors, sarcopenia was specifically associated with an increased risk of significant fibrosis among subgroups with obesity, insulin resistance, metabolic syndrome and liver steatosis (odds ratio 2.37-3.57; all P < 0.05). An independent association between sarcopenia and significant fibrosis was identified after adjusting for other confounders (odds ratio 2.67-3.62 by the nonalcoholic fatty liver disease fibrosis score and 2.04-2.62 by the fibrosis-4 index; all P < 0.05)., Conclusions: Sarcopenia is associated with significant fibrosis in subjects with chronic hepatitis B, specifically those with obesity, insulin resistance, metabolic syndrome and liver steatosis., (© 2018 John Wiley & Sons Ltd.)

Background: A proportion of chronic hepatitis B (CHB) patients are diagnosed with advanced hepatocellular carcinoma (HCC) despite regular surveillance., Aims: To determine predictors for HCC detection failure in CHB patients who underwent regular surveillance., Methods: CHB patients with well-preserved liver function, who underwent ultrasonography and alpha-foetoprotein (AFP) analysis every 6 months, were enrolled. Cox regression analysis was used to identify predictors for detection failure, defined as HCC initially diagnosed at Barcelona Clinic Liver Cancer (BCLC) stage B or C., Results: Of the 4590 CHB patients (mean age, 52.1 years; men, 61.6%), 169 patients were diagnosed with HCC (3.68%) and 35 (20.7%) HCC patients were initially diagnosed with HCC BCLC stage B or C. The cumulative incidence of HCC detection failure was 0.2% at year 1 and 1.3% at year 5. Multivariate analyses indicated that cirrhosis (hazard ratio [HR], 3.078; 95% CI, 1.389-6.821; P = 0.006), AFP levels ≥9 ng/mL (HR, 5.235; 95% CI, 2.307-11.957; P = 0.010), and diabetes mellitus (HR, 3.336; 95% CI, 1.341-8.296; P = 0.010) were independent predictors of HCC detection failure. Another model that incorporated liver stiffness (LS) values identified LS values ≥11.7 kPa (HR, 11.045; 95% CI, 2.066-59.037; P = 0.005) and AFP levels ≥9 ng/mL (HR, 4.802; 95% CI, 1.613-14.297; P = 0.005) as predictors of detection failure., Conclusions: In CHB patients undergoing regular surveillance with ultrasonography and alpha-foetoprotein (AFP) analysis every 6 months, the HCC detection failure rate was not high (0.8% per person; 0.1% per test). However, careful attention should be paid in patients with advanced liver fibrosis (clinical cirrhosis or LS value >11.7 kPa), high AFP levels, or diabetes mellitus, who are prone to surveillance failure., (© 2018 John Wiley & Sons Ltd.)

Analyses using a nationally representative cohort have revealed that high fatty liver index (FLI) is associated with low bone mineral density (BMD) regardless of insulin resistance in men, thereby supporting the deteriorated bone metabolism in nonalcoholic fatty liver disease (NAFLD)., Introduction: NAFLD is linked to deteriorated bone health. We investigated the association of FLI, a scoring model for NAFLD, with BMD., Methods: This was a population-based, cross-sectional study from the Korea National Health and Nutrition Examination Surveys including 4264 Koreans (1908 men and 2356 women). FLI was calculated using body mass index, waist circumference, serum triglyceride, and gamma-glutamyltranspeptidase level. Insulin resistance was evaluated using the homeostasis model assessment-estimated insulin resistance (HOMA-IR) index. BMD was measured using dual-energy X-ray absorptiometry at the lumbar spine, total hip, femoral neck, and whole body., Results: Men had a higher FLI than women, while the HOMA-IR index was similar between men and women. The significant association between FLI and BMD was observed only in men, but not in women. FLI was negatively correlated with total hip, femoral neck, and whole body BMD in men after adjusting for all potential confounders, including HOMA-IR (P < 0.001 to 0.010). Lumbar spine, total hip, femoral neck, and whole body BMD in men showed a decreasing trend as the FLI tertile increased after adjusting for all potential confounders, including HOMA-IR (P for trends < 0.001 to 0.034). In men aged 50 years or older, odds ratios for combined osteopenia and osteoporosis increased across increasing FLI tertiles after adjusting for confounders (P for trends < 0.011 to 0.029)., Conclusion: NAFLD is associated with low bone density regardless of insulin resistance in men. These findings suggest an undiscovered direct link between liver and bone that increases the risk of osteoporosis in men with NAFLD.

Background: This study was conducted in order to compare the strength of scapular elevator and shoulder abductor with and without restricted scapular elevation between male subjects with and without myofascial trigger points in the upper trapezius., Methods: In total, 15 male subjects with myofascial trigger points, and 15age- and weight-matched male subjects without myofascial trigger points in the upper trapezius. Each subject was measured in the strength of maximum isometric scapular elevation and shoulder abduction with and without restricted scapular elevation. Maximum isometric contractions were measured using the Smart KEMA strength measurement system. Independent t-tests were used to compare shoulder strength values between the myofascial trigger points and non- myofascial trigger points groups., Finding: The results showed that shoulder abductor strength in the group with myofascial trigger points (5.64kgf) was significantly lower than in the group without myofascial trigger points (11.96kgf) when scapular elevation was restricted (p<0.05). However, there was no significant difference in the strength of the scapular elevator or shoulder abductor between groups (p>0.05)., Interpretation: These findings suggest that decreased strength in the shoulder abductor with restricted scapular elevation should be considered in evaluating and treating individuals with myofascial trigger points of the upper trapezius., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Aims: To investigate whether preoperative magnetic resonance imaging (MRI) in patients with primary breast cancer is predictive of disease-free (DFS) and overall survival and to determine the prognostic factors indicating survival., Materials and Methods: This retrospective study was approved by the institutional review board and the requirement for informed consent was waived. From 2009 to 2010, 828 women with primary breast cancer and preoperative MRI were matched with 1613 women without such imaging. Patients were matched with regards to 25 patient and tumour-related covariates. A Cox proportional hazards model was used to investigate the time to recurrence and to estimate the hazard ratio for preoperative MRI. Log-rank tests and Cox proportional hazards survival analysis were carried out on total recurrence DFS and overall survival in the unmatched datasets., Results: In total, 799 matched pairs were available for survival analysis. The MRI group showed a tendency towards better survival outcome; however, there were no significant differences in DFS and overall survival. Age at diagnosis (DFS hazard ratio = 0.98; overall survival hazard ratio = 1.04), larger tumour size (DFS hazard ratio = 1.01; overall survival hazard ratio = 1.02), triple negative breast cancer (DFS hazard ratio = 2.64; overall survival hazard ratio = 3.44) and the presence of lymphovascular invasion (DFS hazard ratio = 2.12; overall survival hazard ratio = 2.70) were independent significant variables for worse DFS and overall survival., Conclusion: Preoperative MRI did not result in an improvement in a patient's outcome. Age at diagnosis, tumour size, molecular subtype and lymphovascular invasion were significant independent factors affecting both DFS and overall survival., (Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Some short procedures require deep neuromuscular blockade, which needs to be reversed at the end of the procedure. Forty-four patients undergoing elective laryngeal micro-surgery were randomly allocated into two groups: rocuronium 0.45 mg.kg -1 with neostigmine (50 μg.kg -1 with glycopyrrolate 10 μg.kg -1 ) reversal (moderate block group) vs. rocuronium 0.90 mg.kg -1 with sugammadex (4 mg.kg -1 ) reversal (deep block group). The primary outcome was the intubating conditions during laryngoscopy secondary outcomes included recovery of neuromuscular block; conditions for tracheal intubation; satisfaction score as determined by the surgeon; onset of neuromuscular block; and postoperative sore throat. The onset of neuromuscular block was more rapid, and intubation conditions and ease of intra-operative laryngoscopy were more favourable, and the satisfaction score was lower in the moderate block group compared with the deep block group. No difference was found in the incidence of postoperative sore throat. In laryngeal micro-surgery, the use of rocuronium 0.9 mg.kg -1 with sugammadex for reversal was associated with better surgical conditions and a shorter recovery time than rocuronium 0.45 mg.kg -1 with neostigmine., (© 2017 The Association of Anaesthetists of Great Britain and Ireland.)

A groEL gene-based loop-mediated isothermal amplification (LAMP) assay was developed to detect Vibrio parahaemolyticus in contaminated seafood and water. The assay was optimized and conducted at 63°C for 40 min using Bacillus stearothermophilus (Bst) DNA polymerase, large fragment. Amplification was analysed via multiple detection methods, including opacity, formation of white precipitate, DNA intercalating dyes (ethidium bromide and SYBR Green I), metal ion-binding indicator dye, calcein, and 2% agarose gel electrophoresis. A characteristic ladder-like band pattern on agarose gel and the desired colour changes when using different dyes were observed in positive cases, and these were species-specific for V. parahaemolyticus when compared with other closely related Vibrio spp. The limit of detection (LoD) of this assay was 100 fg per reaction, 100-fold higher than that for conventional polymerase chain reaction (PCR). When tested on artificially contaminated seafood and seawater, the LoDs of the LAMP assay were 120 and 150 fg per reaction respectively, and those of conventional PCR were 120 and 150 pg per reaction respectively. Based on our results, the groEL gene-based LAMP assay is rapid, specific, sensitive, and reliable for detecting V. parahaemolyticus, and it could be used in field diagnosis., Significance and Impact of the Study: The loop-mediated isothermal amplification (LAMP) assay using groEL gene (an abundant, highly conserved gene and member of the groESL chaperone gene family) provided rapid, species-specific and highly sensitive method for detecting Vibrio parahaemolyticus, the leading causal agent of seafood-borne diseases worldwide. Moreover, groEL LAMP revealed high efficiency than conventional PCR assay for V. parahaemolyticus using template both from pure culture and artificially contaminated seafood and water, which indicated the applicability in the field and environmental screening purpose for the organism., (© 2017 The Society for Applied Microbiology.)

It is well established that aging is associated with increased susceptibility to infectious diseases. Fusobacterium nucleatum is a well-known bacterial species that plays a central bridging role between early and late colonizers in the human oral cavity. Further, the ability of F. nucleatum to invade gingival fibroblasts (GFs) is critical to the development of periodontal diseases. However, the mechanisms underlying the age-related infection of GFs by F. nucleatum remain unknown. We used young (fourth passage) and senescent (22nd passage) GFs to investigate the mechanisms of F. nucleatum infection in aged GFs and first observed increased invasion of F. nucleatum in senescent GFs. We also found that the co-localization of caveolin-1 (Cav-1), a protein marker of aging, with F. nucleatum and the knockdown of Cav-1 in GFs reduced F. nucleatum invasion. Additionally, F. nucleatum infection triggered the production of reactive oxygen species (ROS) through activation of NADPH oxidase in GFs, but senescent GFs exhibited significantly lower levels of NADPH oxidase activity and ROS production compared with young GFs in both the uninfected and infected conditions. Also, senescent GFs exhibited a decline in proinflammatory cytokine production and extracellular signal regulated kinase (ERK) phosphorylation following F. nucleatum infection. Interestingly, the knockdown of Cav-1 in senescent GFs increased NADPH oxidase activity and caused the upregulation of interleukin-6 and interleukin-8 and the phosphorylation of ERK. Collectively, the increased expression of Cav-1 might play a critical role in F. nucleatum invasion and could hinder the host response in senescent GFs., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Postmenopausal women with osteoporotic fracture (OF) had higher plasma dipeptidyl-peptidase 4 (DPP4) levels than those without. Furthermore, higher plasma DPP4 levels were significantly associated with higher bone turnover and a higher prevalence of OF. These results indicated that DPP4 may be associated with OF by mediating bone turnover rate., Introduction: Evidence indicates that dipeptidyl-peptidase 4 (DPP4) plays a distinct role in bone metabolism. However, there has been no report on the association, if any, between circulating DPP4 levels and osteoporosis-related phenotypes, including osteoporotic fracture (OF). Therefore, we performed a case-control study to investigate these associations in postmenopausal women., Methods: This study was conducted in multiple centers in Korea. We enrolled 178 cases with OF and 178 age- and body mass index-matched controls. OF was assessed by an interviewer-assisted questionnaire and lateral thoracolumbar radiographs. Bone turnover markers (BTMs), bone mineral density (BMD), and plasma DPP4 levels were obtained in all subjects., Results: After adjustment for potential confounders, subjects with OF had significantly higher DPP4 levels than those without (P = 0.021). Higher DPP4 levels were significantly positively associated with higher levels of all BTMs, but not with BMD at all measured sites. The differences in DPP4 levels according to OF status disappeared after an additional adjustment for each BTM, but not after adjustment for any BMD values. BTMs explained approximately half of the relationship between DPP4 and OF. The risk of OF was 3.80-fold (95% confidence interval = 1.53-9.42) higher in subjects in the highest DPP4 quartile than in those in the lowest quartile after adjustment for potential confounders, including femoral neck BMD., Conclusions: DPP4 may be associated with OF by at least partly mediating the bone turnover rate. Circulating DPP4 levels may be a potential biomarker that could increase the predictive power of current fracture risk assessment models.

We compared the viral suppressive efficacy of tenofovir disoproxil fumarate (TDF) mono-rescue therapy (TDF group) and TDF plus entecavir (ETV) combination-rescue therapy (TDF + ETV group) in chronic hepatitis B (CHB) patients with lamivudine resistance and entecavir resistance. One hundred and thirty-three CHB patients with lamivudine and entecavir resistance were investigated. Ninety-six patients were treated with TDF and 37 with TDF + ETV for at least 6 months. We compared the virologic response rate (HBV DNA level <20 IU/mL) between the two groups and identified the predictive factors of treatment outcome. There were no significant differences between the two groups in demographic characteristics. Up to 24 months [median: 18 (range 6-24) months], 85.4% and 89.2% of the TDF group and TDF + ETV group, respectively, achieved a virologic response (P=.068). Only the HBV DNA level at baseline was significantly associated with a virologic response in the multivariate analysis. In a subanalysis of patients with HBV DNA levels ≥4 log (IU/mL) at baseline, a higher proportion of patients in the TDF + ETV group than the TDF group achieved a virologic response (92.9% vs 68.3%; P<.001), while 90% of patients with HBV DNA (IU/mL) levels <4 log in all both TDF and TDF + ETV groups achieved a virologic response. TDF mono-rescue therapy is a reasonable option in patients with lamivudine resistance and entecavir resistance. However, the combination strategy should be considered in patients with high baseline HBV DNA levels., (© 2016 John Wiley & Sons Ltd.)

In humans, the composition of gut commensal bacteria is closely correlated with obesity. The bacteria modulate metabolites and influence host immunity. In this study, we attempted to determine whether there is a direct correlation between specific commensal bacteria and host metabolism. As mice aged, we found significantly reduced body weight and fat mass in Atg7 ΔCD11c mice when compared with Atg7 f/f mice. When mice shared commensal bacteria by co-housing or feces transfer experiments, body weight and fat mass were similar in both mouse groups. By pyrosequencing analysis, Bacteroides acidifaciens (BA) was significantly increased in feces of Atg7 ΔCD11c mice compared with those of control Atg7 f/f mice. Wild-type C57BL/6 (B6) mice fed with BA were significantly more likely to gain less weight and fat mass than mice fed with PBS. Of note, the expression level of peroxisome proliferator-activated receptor alpha (PPARα) was consistently increased in the adipose tissues of Atg7 ΔCD11c mice, B6 mice transferred with fecal microbiota of Atg7 ΔCD11c mice, and BA-fed B6 mice. Furthermore, B6 mice fed with BA showed elevated insulin levels in serum, accompanied by increased serum glucagon-like peptide-1 and decreased intestinal dipeptidyl peptidase-4. These finding suggest that BA may have potential for treatment of metabolic diseases such as diabetes and obesity.

Background: In patients with chronic hepatitis B, tenofovir disoproxil fumarate (TDF) plus pegylated interferon (PEG-IFN) for 48-weeks results in higher rates of hepatitis B surface antigen (HBsAg) loss than either monotherapy., Aim: To identify baseline and on-treatment factors associated with HBsAg loss at Week 72 and provide a model for predicting HBsAg loss in patients receiving combination therapy for 48 weeks., Methods: A secondary analysis of data from an open-label study where patients were randomised to TDF (300 mg/day, oral) plus PEG-IFN (PI, 180 μg/week, subcutaneous) for 48 weeks (TDF/PI-48w); TDF plus PEG-IFN for 16 weeks, TDF for 32 weeks (TDF/PI-16w+TDF-32w); TDF for 120 weeks (TDF-120w) or PEG-IFN for 48 weeks (PI-48w). Logistic regression methods were used to identify models that best predicted HBsAg loss at Week 72., Results: Rates of HBsAg loss at Week 72 were significantly higher in the TDF/PI-48w group (6.5%) than in the TDF/PI-16w+TDF-32w (0.5%), TDF-120w (0%) and PI-48w (2.2%) groups (P = 0.09). The only baseline factor associated with response was genotype A. HBsAg decline at Week 12 or 24 of treatment was associated with HBsAg loss at Week 72 (P < 0.001). HBsAg decline >3.5 log 10 IU/mL at Week 24 in the TDF/PI-48w group resulted in a positive predictive value of 85% and a negative predictive value of 99% for HBsAg loss at Week 72., Conclusions: HBsAg decline at Week 24 of TDF plus PEG-IFN combination therapy may identify patients who, after completing 48 weeks of treatment, have a better chance of achieving HBsAg loss at Week 72., (© 2016 John Wiley & Sons Ltd.)

Aim: Nonalcoholic hepatic fat accumulation has been hypothesized to be associated with alterations in gut microbiota composition, although mechanistic explanations for this link are largely insufficient. The aim of this study was to elucidate the microbiota-driven mechanisms involved in the development of nonalcoholic hepatic steatosis., Methods and Results: Ob/ob mice and their wild-type lean control mice were fed an AIN-93G diet for 12 weeks. Faecal microbiota composition, faecal bile acid (BA) profile and intestinal and hepatic markers of BA metabolism were analysed. Ob/ob mice had significantly less faecal taurine-conjugated BAs compared to their lean controls. The proportions of butyrate-producing bacteria were lower in ob/ob mice compared to those in lean mice. Intestinal expression of farnesoid X receptor (FXR) mRNA was significantly higher, whereas hepatic expression of cholesterol-7α-hydroxylase 1 (CYP7A1) and small heterodimer partner (SHP) were significantly lower in ob/ob mice compared to those in control mice., Conclusion: Microbiota-associated BAs deconjugation may induce nonalcoholic fatty liver disease (NAFLD) by activating intestinal FXR signalling and blocking hepatic FXR-SHP pathway, thereby accelerating fat synthesis., Significance and Impact of the Study: We provided evidences that changes in the gut microbiota and their metabolites can alter the profile of BAs, thereby providing a mechanism by which an altered microbiota profile contributes to the development of NAFLD., (© 2016 The Society for Applied Microbiology.)

Non-gestational choriocarcinoma (NGCO) is a rare primary ovarian cancer with poor prognosis. It is important to distinguish it from gestational ovarian choriocarcinoma (GCO), because there are different treatment options. However, it is difficult to distinguish the two types by routine histologic, ultrastructural, or immunohistochemical examination. The authors present NGCO in a 41-year-old woman, which was confirmed by DNA polymorphism analysis. All tested microsatellite markers had identical DNA profiles with the same allelic sizes between tumor and normal myometrium of the patient, indicating that both tissues originated from the same person. The results confirmed that the tumor was non-gestational in origin. Although the tumor was large, the authors performed hand- assisted laparoscopic surgical (HALS) staging. After three cycles of combination chemotherapy and surgery, the patient has not had any evidence of disease 48 months after treatment. This case demonstrates the usefulness of HALS staging and DNA polymorphism analysis in NGCO.

Unlabelled: A high level of circulating sphingosine-1-phosphate (S1P) is associated with a high incidence of osteoporotic fracture and a high rate of an insufficient response to bisphosphonate therapy., Introduction: Sphingosine-1-phosphate (S1P) is a significant regulator of bone metabolism. Recently, we found that a high plasma S1P level is associated with low bone mineral density (BMD), high levels of bone resorption markers (BRMs), and a high risk of prevalent vertebral fracture in postmenopausal women. We investigated the possibility that S1P is a predictor of incident fracture., Methods: A total of 248 postmenopausal women participated in this longitudinal study and were followed up for a mean duration of 3.5 years (untreated [n = 76] or treated with bisphosphonate or hormone replacement therapy [n = 172]). The baseline plasma S1P level and prevalent and incident fracture occurrence were assessed., Results: A high S1P level was significantly associated with a higher rate of prevalent fracture after adjusting for femoral neck (FN) BMD, BRM, and potential confounders (odds ratio = 2.05; 95 % confidence interval [CI] = 1.03-4.00). Incident fractures occurred more frequently in the highest S1P tertile (T3) than in the lower two tertiles (T1-2) after adjusting for confounders, including baseline FN BMD, prevalent fracture, antiosteoporotic medication, annualized changes in FN BMD, BRM, and potential confounders (hazard ratio = 5.52; 95 % CI = 1.04-56.54). Insufficient response to bisphosphonate therapy occurred more frequently in T3 than T1-2 (odds ratio = 4.43; 95 % CI = 1.02-21.25)., Conclusions: The plasma S1P level may be a potential predictor of fracture occurrence and an insufficient response to bisphosphonate therapy in postmenopausal women.

In Korea, patients with chronic hepatitis C virus (HCV) infection are typically treated with pegylated interferon-alpha plus ribavirin, but interferons are contraindicated in many patients and are often poorly tolerated, particularly by the elderly and those with advanced liver disease. No interferon-free treatment regimens are approved in Korea. Sofosbuvir is an oral nucleotide analog inhibitor of the HCV nonstructural 5B RNA polymerase. It is approved in the USA, European Union and Japan for treating a number of HCV genotypes, including genotype 2. Genotype 2 has a seroprevalence of 38-46% in Korea. This single-arm, phase 3b study (NCT02021643) examined the efficacy and safety of sofosbuvir plus ribavirin (12-week duration) in chronic genotype 2 HCV-infected treatment-naive and treatment-experienced Korean patients with and without cirrhosis. The proportion of patients with sustained virologic response 12 weeks after treatment discontinuation (SVR12) was 97% (125/129), with 96% (101/105) of treatment-naive and 100% (24/24) of treatment-experienced patients achieving SVR12. Two patients experienced virologic failure (n = 1, on-treatment failure; n = 1, relapse). No patient discontinued study treatment due to an adverse event (AE). The most common treatment-emergent AEs were headache (18%, 23/129) and pruritus (15%, 19/129). Few patients had grade 3 AEs (5%, 6/129) or grade 3 laboratory abnormalities (12%, 15/129). No grade 4 AE was reported. These data suggest that 12 weeks of treatment with the all-oral, interferon-free regimen of sofosbuvir plus ribavirin is effective and well tolerated in Korean patients with chronic genotype 2 HCV infection., (© 2016 The Authors. Journal of Viral Hepatitis Published by John Wiley & Sons Ltd.)

Patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) have suppressed TLR2 expression, function and cytokine production. The aim of this study was to explore the importance of hepatitis B virus (HBV) genotype in innate immune responses and investigate whether Toll-like receptor (TLR) expression/function has potential roles as predictive biomarkers of successful therapy with pegylated interferon (Peg-IFN) therapy of HBeAg seroconversion in HBeAg-positive patients. We showed that as early as 4 weeks after initiation of Peg-IFN, future HBeAg seroconverters had significantly elevated levels of TLR2 expression on monocytes. TLR2-associated IL-6 production at baseline and week 4 of therapy and TLR4 IL-6 production at week 4 were also markedly elevated in HBeAg seroconverters. HBV genotype also influenced treatment response, with genotypes A and B more likely to seroconvert than D. We were able to demonstrate that these differences were due in part to the interaction of the specific HBeAg proteins with TLR pathway adaptor molecules, and these interactions were genotype dependent. HBeAg-mediated modulation of TLR signalling was also observed in Huh7 cells, following stimulation with Pam3Cys. Importantly, the addition of IFN-α to TLR2-stimulated cells cotransfected with an HBeAg expression plasmid reversed HBeAg-mediated suppression of hepatocytes. These findings demonstrate that patients with an activated inflammatory response are much more likely to respond to IFN therapy, with TLR responses showing promise as potential biomarkers of HBeAg seroconversion in this setting. Furthermore, our findings suggest there is differential genotype-specific HBeAg suppression of innate signalling pathways which may account for some of the clinical differences observed across the CHB spectrum., (© 2015 John Wiley & Sons Ltd.)

Background: Although recent studies provide clinical evidence that sphingosine-1-phosphate (S1P) may primarily affect bone resorption in humans, rather than bone formation or the osteoclast-osteoblast coupling phenomenon, those studies could not determine which bone resorption mechanism is more important, i.e., chemorepulsion of osteoclast precursors via the blood to bone marrow S1P gradient or receptor activator of NF-κB ligand (RANKL) elevation in osteoblasts via local S1P., Aim: To investigate how S1P mainly contributes to increased bone resorption in humans, we performed this case-control study at a clinical unit in Korea., Methods: Blood and bone marrow samples were contemporaneously collected from 70 patients who underwent hip surgery due to either osteoporotic hip fracture (HF) (n = 10) or other causes such as osteoarthritis (n = 60)., Results: After adjusting for sex, age, BMI, smoking, alcohol, previous fracture, diabetes, and stroke, subjects with osteoporotic HF demonstrated a 3.2-fold higher plasma/bone marrow S1P ratio than those without HF, whereas plasma and bone marrow S1P levels were not significantly different between these groups. Consistently, the risk of osteoporotic HF increased 1.38-fold per increment in the plasma/bone marrow S1P ratio in a multivariate adjustment model. However, the odds ratios for prevalent HF according to the increment in the plasma and bone marrow S1P level were not statistically significant., Conclusion: Our current results using simultaneously collected blood and bone marrow samples suggest that the detrimental effects of S1P on bone metabolism in humans may depend on the S1P gradient between the peripheral blood and bone marrow cavity.

Extracellular Matrix Protein 1 (ECM1) is a marker for tumorigenesis and is correlated with invasiveness and poor prognosis in various types of cancer. However, the functional role of ECM1 in cancer metastasis is unclear. Here, we detected high ECM1 level in breast cancer patient sera that was associated with recurrence of tumor. The modulation of ECM1 expression affected not only cell migration and invasion, but also sphere-forming ability and drug resistance in breast cancer cell lines. In addition, ECM1 regulated the gene expression associated with the epithelial to mesenchymal transition (EMT) progression and cancer stem cell (CSC) maintenance. Interestingly, ECM1 increased β-catenin expression at the post-translational level through induction of MUC1, which was physically associated with β-catenin. Indeed, the association between β-catenin and the MUC1 cytoplasmic tail was increased by ECM1. Furthermore, forced expression of β-catenin altered the gene expression that potentiated EMT progression and CSC phenotype maintenance in the cells. These data provide evidence that ECM1 has an important role in cancer metastasis through β-catenin stabilization.

Background: It was recently reported that G protein-coupled receptor 65 (GPR65) suppresses ovariectomy-induced bone loss., Aim: The present study investigated the role of the lysosphingolipid psychosine, a GPR65 ligand, on osteoclastic differentiation and bone resorption., Methods: Osteoclasts were differentiated from mouse bone marrow macrophages. Tartrate-resistant acid phosphatase-positive multinucleated cells were considered to be osteoclasts, and the resorption area was measured by incubating the cells on dentine discs. The expression levels of osteoclast differentiation markers were assessed by qRT-PCR. GPR65 siRNA and its scrambled siRNA were transfected with lipofectamine. Intracellular cyclic adenosine monophosphate (cAMP) levels were assessed using a direct enzyme immunoassay., Results: Psychosine inhibited osteoclastogenesis and in vitro bone resorption without any significant effect on the viability of pre-osteoclasts, decreased the expression of osteoclast differentiation markers significantly, and increased intracellular cAMP levels. The knockdown of GPR65 by its siRNA restored osteoclastogenesis and decreased cAMP levels in the presence of psychosine., Conclusion: Psychosine inhibits osteoclastogenesis by increasing intracellular cAMP levels via GPR65.

Formation of magnetite in anaerobic sediments is thought to be enhanced by the activities of iron-reducing bacteria. Geobacter has been implicated as playing a major role, as in culture its cells are often associated with extracellular magnetite grains. We studied the bacterial community associated with magnetite grains in sediment of a freshwater pond in South Korea. Magnetite was isolated from the sediment using a magnet. The magnetite-depleted fraction of sediment was also taken for comparison. DNA was extracted from each set of samples, followed by PCR for 16S bacterial ribosomal RNA (rRNA) gene and HiSeq sequencing. The bacterial communities of the magnetite-enriched and magnetite-depleted fractions were significantly different. The enrichment of three abundant operational taxonomic units (OTUs) suggests that they may either be dependent upon the magnetite grain environment or may be playing a role in magnetite formation. The most abundant OTU in magnetite-enriched fractions was Geobacter, bolstering the case that this genus is important in magnetite formation in natural systems. Other major OTUs strongly associated with the magnetite-enriched fraction, rather than the magnetite-depleted fraction, include a Sulfuricella and a novel member of the Betaproteobacteria. The existence of distinct bacterial communities associated with particular mineral grain types may also be an example of niche separation and coexistence in sediments and soils, which cannot usually be detected due to difficulties in separating and concentrating minerals.

Summary: Data gathered from a nationally representative cohort demonstrated that subject with low skeletal muscle mass had consistently low femoral neck composite strength indices for compression, bending, and impact, especially in older women, supporting the highly integrated nature of skeletal muscle and bone., Introduction: Skeletal muscle and bone interact mechanically and functionally. The present study was performed to investigate the association between muscle mass and femoral neck composite strength indices using a nationally representative cohort., Methods: This is a population-based, cross-sectional study from Korea National Health and Nutrition Examination Surveys, including 1,275 Koreans (674 women and 601 men) aged 50 years or older. Femoral neck axis length and width were measured by hip DXA scans and were combined with BMD, body weight, and height to create composite indices of femoral neck strength relative to load in three different failure modes: compression, bending, and impact. Presarcopenia was defined as an appendicular skeletal muscle mass (ASM) divided by body weight that was less than 1 SD below the sex-specific mean for young adults., Results: After adjusting for confounders, women with presarcopenia had consistently lower indices for compression strength (CSI), bending strength (BSI), and impact strength (ISI) than women without this condition. Men with presarcopenia had a lower ISI value than men without presarcopenia. Multiple regression analyses revealed that lower relative skeletal muscle mass (ASM/weight) associated significantly with lower values for all three femoral neck composite indices in women and with lower CSI and ISI in men., Conclusions: These findings provide the first clinical evidence for the notion that age-related low muscle mass may increase the risk of osteoporotic hip fractures by decreasing femoral neck strength relative to load, especially in older women, and support the highly integrated nature of skeletal muscle and bone.

Neoadjuvant endocrine therapy is an alternative to chemotherapy for women with oestrogen receptor (ER)-positive early breast cancer (BC). We aimed to assess feasibility of recruiting patients to a study comparing chemotherapy versus endocrine therapy in postmenopausal women with ER-rich primary BC, and response as well as translational endpoints were assessed. Patients requiring neoadjuvant therapy were randomised to chemotherapy: 6 × 3-weekly cycles FE₁₀₀C or endocrine therapy: letrozole 2.5 mg, daily for 18-23 weeks. Primary endpoints were recruitment feasibility and tissue collection. Secondary endpoints included clinical, radiological and pathological response rates, quality of life and translational endpoints. 63/80 patients approached were eligible, of those 44 (70, 95% CI 57-81) were randomised. 12 (54.5, 95% CI 32.2-75.6) chemotherapy patients showed radiological objective response compared with 13 (59.1, 95% CI 36.4-79.3) letrozole patients. Compared with baseline, mean Ki-67 levels fell in both groups at days 2-4 and at surgery [fold change: 0.24 (95% CI 0.12-0.51) and 0.24; (95% CI 0.15-0.37), respectively]. Plasma total cfDNA levels rose from baseline to week 8 [fold change: chemotherapy 2.10 (95% CI 1.47-3.00), letrozole 1.47(95% CI 0.98-2.20)], and were maintained at surgery in the chemotherapy group [chemotherapy 2.63; 95% CI 1.56-4.41), letrozole 0.95 (95% CI 0.71-1.26)]. An increase in plasma let-7a miRNA was seen at surgery for patients with objective radiological response to chemotherapy. Recruitment and tissue collection endpoints were met; however, a larger trial was deemed unfeasible due to slow accrual. Both regimens were equally efficacious. Dynamic changes were seen in Ki-67 and circulating biomarkers in both groups with increases in cfDNA and let-7a miRNA persisting until surgery for chemotherapy patients.

This study compared the molecular characteristics of vancomycin-resistant Enterococcus faecium (VREF) isolates recovered from 20 non-tertiary-care hospitals (36 isolates) and three tertiary-care hospitals (26 isolates) in diverse geographical areas of Korea from October 2010 to April 2011. All isolates carried the vanA gene only, but 42% and 73% of non-tertiary and tertiary-care isolates expressed the VanB phenotype (teicoplanin minimum inhibitory concentration ⩽16 μg/ml). All isolates harboured insertion sequences, IS1542 and IS1216V, within Tn1546. The isolates from tertiary-care hospitals tended to have reduced Tn1546 lengths by deletion of sequences adjacent to IS elements. Multilocus sequence typing revealed eight sequence types within clonal complex 17 (CC17), but DNA fingerprinting by rep-PCR did not show clonal relatedness between the intra- and inter-hospital isolates. These results suggest that vanA, which has prevailed in tertiary-care hospitals of Korea since the 1990s, had been transferred horizontally to non-tertiary-care hospitals while the genetic rearrangement driven by evolutionary adaptation to adverse environments may have occurred in tertiary-care hospitals.

Unlabelled: The mechanisms by which hepatitis B virus (HBV) establishes and maintains chronic hepatitis B infection (CHB) are poorly defined. Innate immune responses play an important role in reducing HBV replication and pathogenesis. HBV has developed numerous mechanisms to escape these responses, including the production of the secreted hepatitis B e antigen (HBeAg), which has been shown to regulate antiviral toll-like receptor (TLR) and interleukin-1 (IL-1) signaling. IL-18 is a related cytokine that inhibits HBV replication in hepatoma cell lines and in the liver through the induction of gamma interferon (IFN-γ) by NK cells and T cells. We hypothesized that HBV or HBV proteins inhibit IFN-γ expression by NK cells as an accessory immunomodulatory function. We show that HBeAg protein inhibits the NF-κB pathway and thereby downregulates NK cell IFN-γ expression. Additionally, IFN-γ expression was significantly inhibited by exposure to serum from individuals with HBeAg-positive but not HBeAg-negative chronic HBV infection. Further, we show that the HBeAg protein suppresses IL-18-mediated NF-κB signaling in NK and hepatoma cells via modulation of the NF-κB pathway. Together, these findings show that the HBeAg inhibits IL-18 signaling and IFN-γ expression, which may play an important role in the establishment and/or maintenance of persistent HBV infection., Importance: It is becoming increasingly apparent that NK cells play a role in the establishment and/or maintenance of chronic hepatitis B infection. The secreted HBeAg is an important regulator of innate and adaptive immune responses. We now show that the HBeAg downregulates NK cell-mediated IFN-γ production and IL-18 signaling, which may contribute to the establishment of infection and/or viral persistence. Our findings build on previous studies showing that the HBeAg also suppresses the TLR and IL-1 signaling pathways, suggesting that this viral protein is a key regulator of antiviral innate immune responses., (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)

Unlabelled: In this large longitudinal study of 16,078 Korean men aged 50 years or older, we observed that baseline elevation of serum uric acid level significantly associated with a lower risk of incident fractures at osteoporosis-related sites during an average follow-up period of 3 years., Introduction: Male osteoporosis and related fractures are becoming recognized as important public health concerns. Oxidative stress has detrimental effects on bone metabolism, and serum uric acid (UA) is known to be a strong endogenous antioxidant. In the present study, we performed a large longitudinal study with an average follow-up period of 3 years to clarify the role of UA on the risk of incident osteoporotic fractures (OFs)., Methods: A total of 16,078 Korean men aged 50 years or older who had undergone comprehensive routine health examinations were enrolled. Incident fractures at osteoporosis-related sites (e.g., hip, spine, distal radius, and proximal humerus) that occurred after the baseline examinations were identified from the nationwide claims database of the Health Insurance Review and Assessment Service of Korea by using selected International Classification of Diseases, 10th revision codes., Results: In total, 158 (1.0 %) men developed incident OFs. The event rate was 33.1 per 10,000 person-years. Subjects without incident OFs had 6.0 % higher serum UA levels than subjects with OFs (P = 0.001). Multivariable-adjusted Cox proportional hazard analyses adjusted for age, body mass index, glomerular filtration rate, lifestyle factors, medical and drug histories, and the presence of baseline radiological vertebral fractures revealed that the hazard ratio per standard deviation increase of baseline UA levels for the development of incident OFs was 0.829 (95 % CI = 0.695-0.989, P = 0.038)., Conclusions: These data provide the epidemiological evidence that serum UA may act as a protective factor against the development of incident OFs in Korean men.

Unlabelled: Higher serum uric acid (UA) was associated with higher bone mass, lower bone turnover, and lower prevalence of vertebral fracture in postmenopausal women. Furthermore, UA suppressed osteoclastogenesis and decreased production of reactive oxygen species in osteoclast precursors, indicating UA may have beneficial effects on bone metabolism as an antioxidant., Introduction: UA is known to play a physiological role as an antioxidant, and oxidative stress has detrimental effects on bone metabolism. In the present study, we investigated the association of serum UA level with the osteoporosis-related phenotypes and its direct effect on bone-resorbing osteoclasts using in vitro systems., Methods: This is a large cross-sectional study, including 7,502 healthy postmenopausal women. Bone mineral density (BMD) and serum UA concentrations were obtained from all subjects. Data on bone turnover markers and lateral thoracolumbar radiographs were available for 1,023 and 6,918 subjects, respectively. An in vitro study investigated osteoclastogenesis and reactive oxygen species (ROS) levels according to UA treatment., Results: After adjusting for multiple confounders, serum UA levels were positively associated with BMD at all sites (all p < 0.001). Compared with the participants in the highest UA quartile, the odds for osteoporosis were 40 % higher in those in the lowest quartile. The serum UA levels were inversely related to both serum C-terminal telopeptide of type I collagen and osteocalcin levels (p < 0.001 and p = 0.004, respectively). Consistently, subjects with vertebral fracture had lower serum UA levels, compared with those without it (p = 0.009). An in vitro study showed that UA decreased osteoclastogenesis in a dose-dependent manner and reduced the production of ROS in osteoclast precursors., Conclusion: These results provide epidemiological and experimental evidence that serum UA may have a beneficial effect on bone metabolism as an antioxidant in postmenopausal women.

Background: This study was undertaken to investigate risk factors of mortality in patients with fulminant hepatic failure (FHF)., Methods: Fifty-three patients with FHF treated from January 2006 to April 2011 were allocated to a spontaneous survival group (group 1), a death without liver transplantation (LT) group (group 2), and an LT group (group 3). To analyze risk factors associated with mortality in FHF, we excluded group 3 patients. Clinical features, Model for End-Stage Liver Disease (MELD) scores, and King's College Hospital criteria at the time of hepatic encephalopathy in group 2 were compared with those of group 1., Results: The causes of FHF were acute viral infection (n = 29, hepatitis A:B, 28:1), drugs (n = 18; including 4 acetaminophen and 14 herbal medication), autoimmune (n = 4), and miscellaneous (n = 2). Of the 53 patients, 19 were allocated to group 1, 18 to group 2, and 16 to group 3. According to univariate analysis, risk factors for mortality in group 2 were acute renal failure requiring renal replacement therapy and a MELD score ≥30 at the time of hepatic encephalopathy. However, by multivariate analysis, a MELD score ≥30 was the only independent risk factor for mortality in group 2 (P = .042; hazard ratio, 4.500)., Conclusions: A MELD score ≥30 was found to be the only independent risk factor of mortality in FHF patients without LT. Therefore, the findings of this study suggest that these patients may need emergent LT for survival., (Copyright © 2013. Published by Elsevier Inc.)

Unlabelled: Although the presence of metabolic syndrome (MetS) and increasing numbers of MetS components were associated with attenuated bone loss at various skeletal sites in postmenopausal women, this beneficial effect of MetS on bone mass can be mainly explained by higher mechanical loading in the affected subjects., Introduction: Previous cross-sectional epidemiological studies reported the inconsistent results regarding the combined effects of MetS on bone mass. In our present report, we performed a large, longitudinal study to evaluate MetS in relation to annualized bone mineral density (BMD) changes in postmenopausal Korean women., Methods: The study cohort consisted of 1,218 postmenopausal women who had undergone comprehensive routine health examinations with an average follow-up interval of 3 years. The BMD at the lumbar spine and proximal femur sites was measured with dual-energy X-ray absorptiometry using the same equipment at baseline and at follow-up., Results: Following adjustment for age, baseline BMD, and lifestyle factors, the women with MetS had 21.7, 17.0, 26.7, and 31.1 % less bone loss at the total femur, femur neck, trochanter, and lumbar spine, respectively, compared with MetS-free women (P = 0.004 to 0.041). Consistently, the rates of bone loss at all skeletal sites were linearly attenuated with increasing numbers of MetS components (P = 0.004 to <0.001). Importantly, when weight and height were added as confounding factors, the differences and trends of annualized BMD changes according to the MetS status disappeared., Conclusion: Our current results indicate that the beneficial effects of MetS on bone mass can be mainly explained by higher mechanical loading in the affected subjects. Consequently, MetS per se may not be a meaningful concept for predicting future bone loss and for explaining associations between osteoporosis and cardiovascular diseases.

Background: It remains unclear whether initial compact lipiodol uptake after transarterial chemoembolisation (TACE) is associated with improved survival in patients with hepatocellular carcinoma (HCC)., Aim: To reveal the clinical relevance of compact lipiodolisation after TACE., Methods: We studied 490 patients with unresectable HCC who had first been treated with TACE. Compact lipiodolisation was defined as the absence of an arterial enhancing lesion, reflecting complete lipiodol uptake, as assessed by dynamic computed tomography (CT) 1 month after treatment. The rate of initial compact lipiodolisation was analysed according to multiplicity and size of tumour, and survival of patients who achieved compact lipiodolisation was compared to that of patients who did not., Results: Of the 490 patients, 409 (83.5%) were in Child-Pugh class A and 81 (16.5%) in class B. The rate of initial compact lipiodolisation in single HCCs was higher than that in multinodular HCCs (33.7% vs. 14.6%, P < 0.001). Among single HCCs, the rate of compact lipiodolisation in tumours ≤5, 5-10 and >10 cm was 46.6%, 13.6%, and 0% respectively. The 1-, 3- and 5-year survival rates of patients with compact uptake were 92.7%, 70.7% and 52.4% compared to 60.8%, 28.0% and 16.9% in patients with noncompact lipiodolisation. Multivariate analysis revealed that Child-Pugh class, alpha-fetoprotein level, tumour node metastasis stage, portal vein thrombosis and initial compact lipiodolisation were independent predictors of survival., Conclusions: Initial compact lipiodol uptake after transarterial chemoembolisation is associated with improved survival in patients with unresectable hepatocellular carcinoma. Accordingly, initial complete lipiodolisation should be considered a relevant therapeutic target., (© 2012 Blackwell Publishing Ltd.)

The best examples of halo nuclei, exotic systems with a diffuse nuclear cloud surrounding a tightly bound core, are found in the light, neutron-rich region, where the halo neutrons experience only weak binding and a weak, or no, potential barrier. Modern direct-reaction measurement techniques provide powerful probes of the structure of exotic nuclei. Despite more than four decades of these studies on the benchmark one-neutron halo nucleus 11Be, the spectroscopic factors for the two bound states remain poorly constrained. In the present work, the 10Be(d,​p) reaction has been used in inverse kinematics at four beam energies to study the structure of 11Be. The spectroscopic factors extracted using the adiabatic model were found to be consistent across the four measurements and were largely insensitive to the optical potential used. The extracted spectroscopic factor for a neutron in an nℓj=2s(1/2) state coupled to the ground state of 10Be is 0.71(5). For the first excited state at 0.32 MeV, a spectroscopic factor of 0.62(4) is found for the halo neutron in a 1p(1/2) state.

Background and Purpose: Radiologic methods for the diagnosis of chemical radiculitis associated with anular tears in the lumbar spine have been rare. Provocative diskography is one of the methods for diagnosing diskogenic chemical radiculitis but is invasive. A reliable imaging method for replacing provocative diskography and diagnosing chemical radiculitis is required. Our aim was to investigate the value of 3D MR radiculography depicted by rendering imaging in the diagnosis of symptomatic chemical radiculopathy associated with anular tears., Materials and Methods: The study population consisted of 17 patients (age range, 32-88 years) with unilateral radiculopathy. Symptomatic chemical radiculopathy was confirmed with provocative CT diskography and/or provocative selective nerve root block for agreement of sides and levels. Through adhering to the principles of selective excitation (Proset imaging), we acquired 3D coronal FFE sequences with selective water excitation. Morphologic changes in the ipsilateral symptomatic nerve root caused by chemical radiculopathy were compared with those in the contralateral nerve root on 3D MR lumbosacral radiculography., Results: Pain reproduction at the contrast-leak level during diskography (n = 4) and selective nerve root injection (n = 13) showed concordant pain in all patients. All patients with symptomatic chemical radiculopathy showed nerve root swelling in both ipsilateral levels and sides on 3D MR radiculography. The most common nerve root affected by the chemical radiculopathy was the L5 nerve root (n = 13), while the most common segment exhibiting nerve root swelling was the exit nerve root (n = 16)., Conclusions: All patients with radicular leg pain caused by chemical radiculopathy showed nerve root swelling on 3D MR radiculography. We believe that in cases without mechanical nerve root compression caused by disk herniation or stenosis in the lumbar spine, nerve root swelling on 3D MR radiculography in patients with radiculopathy associated with an anular tear may be relevant in the diagnosis of symptomatic chemical radiculopathy.

Background: Interleukin (IL)-33 is involved in the Th2 immune response and could play an essential role in nasal allergy. Therefore, we aimed to investigate the therapeutic potential of anti-IL-33 for allergic rhinitis (AR)., Methods: Twenty-four BALB/c mice were used. In group A (control group, n = 6), mice were sensitized and challenged with saline. Group B [ovalbumin (OVA) group, n = 6] mice received intraperitoneal and intranasal OVA challenge. In group C (control IgG group, n = 6), mice were injected intraperitoneally with rabbit control IgG before OVA challenge. In group D (anti-IL-33 group, n = 6), anti-IL-33 was injected before challenge. We evaluated the number of nose-scratching events and external morphology; serum total and OVA-specific IgE; number of eosinophils, neutrophils, and lymphocytes in bronchoalveolar lavage (BAL) fluid; histopathologic examination of nasal cavity; and IL-4, IL-5, and IL-13 in BAL fluid., Results: Anti-IL-33 treatment significantly reduced the nose-scratching events and ameliorated skin denudation. Serum total and OVA-specific IgE was significantly decreased in group D. The number of eosinophils in BAL fluid was also significantly decreased. Eosinophilic infiltration in the nasal cavity was significantly decreased in group D. IL-4, IL-5, and IL-13 in BAL fluid were also significantly decreased after treatment., Conclusions: Anti-IL-33 antibody has a therapeutic potential for experimental AR., (© 2011 John Wiley & Sons A/S.)

Objectives: The purpose of this study was to determine the relative accuracies of mammography, sonography, MRI and clinical examination in predicting residual tumour size and pathological response after neoadjuvant chemotherapy for locally advanced or inflammatory breast cancer. Each prediction method was compared with the gold standard of surgical pathology., Methods: 43 patients (age range, 25-62 years; mean age, 42.7 years) with locally advanced or inflammatory breast cancer who had been treated by neoadjuvant chemotherapy were enrolled prospectively. We compared the predicted residual tumour size and the predicted response on imaging and clinical examination with residual tumour size and response on pathology. Statistical analysis was performed using weighted kappa statistics and intraclass correlation coefficients (ICC)., Results: The ICC values between predicted tumour size and pathologically determined tumour size were 0.65 for clinical examination, 0.69 for mammography, 0.78 for sonography and 0.97 for MRI. Agreement between the response predictions at mid-treatment and the responses measured by pathology had kappa values of 0.28 for clinical examination, 0.32 for mammography, 0.46 for sonography and 0.68 for MRI. Agreement between the final response predictions and the responses measured by pathology had kappa values of 0.43 for clinical examination, 0.44 for mammography, 0.50 for sonography and 0.82 for MRI., Conclusion: Predictions of response and residual tumour size made on MRI were better correlated with the assessments of response and residual tumour size made upon pathology than were predictions made on the basis of clinical examination, mammography or sonography. Thus, the evaluation of predicted response using MRI could provide a relatively sensitive early assessment of chemotherapy efficacy.

Objectives: The purpose of this study was to correlate sonographic and mammographic findings with prognostic factors in patients with node-negative invasive breast cancer., Methods: Sonographic and mammographic findings in 710 consecutive patients (age range 21-81 years; mean age 49 years) with 715 node-negative invasive breast cancers were retrospectively evaluated. Pathology reports relating to tumour size, histological grade, lymphovascular invasion (LVI), extensive intraductal component (EIC), oestrogen receptor (ER) status and HER-2/neu status were reviewed and correlated with the imaging findings. Statistical analysis was performed using logistic regression analysis and intraclass correlation coefficient (ICC)., Results: On mammography, non-spiculated masses with calcifications were associated with all poor prognostic factors: high histological grade, positive LVI, EIC, HER-2/neu status and negative ER. Other lesions were associated with none of these poor prognostic factors. Hyperdense masses on mammography, the presence of mixed echogenicity, posterior enhancement, calcifications in-or-out of masses and diffusely increased vascularity on sonography were associated with high histological grade and negative ER. Associated calcifications on both mammograms and sonograms were correlated with EIC and HER-2/neu overexpression. The ICC value for the disease extent was 0.60 on mammography and 0.70 on sonography., Conclusion: Several sonographic and mammographic features can have a prognostic value in the subsequent treatment of patients with node-negative invasive breast cancer. Radiologists should pay more attention to masses that are associated with calcifications because on both mammography and sonography associated calcifications were predictors of positive EIC and HER-2/neu overexpression.